Transcriptionally regulated adenoviruses for prostate-specific gene therapy

Yi Lu, Mitchell S. Steiner

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Most virally based vectors for gene therapy contain viral promoters that are tissue-nonspecific. Consequently, unintended expression of toxic therapeutic genes in normal tissues may potentially occur. We have constructed adenoviruses that contain a bacterial /?-galactosidase (/?-gal) gene (lacZ) under the control of three different prostate-specific promoters: prostatespecific antigen (PSA), probasin, and the mouse mammary-tumor-virus long terminal repeat (MMTV; prostate-specific Ad-lacZ). In general, these prostatespecific Ad-lacZ can effectively transduce and express -gal in prostate cells and display weak, if any, expression of/?-gal in nonprostate cells in vitro. In vivo, these adenoviruses showed a high level of /?-gal expression in canine prostate but also disseminated to tissues other than prostate after intraprostatic (i.p.) injection. However, none of the prostate-specific Ad-lacZ expressed -ga\ in these nonprostate tissues. Furthermore, prostate-specific Ad-lacZ expressed /?-gal only in xenograft tumors grown in nude mice, derived from human prostate-cancer cells DU 145 and PPC-1, but showed no -gal expression in tumors derived from human bladder-cancer cells RT4. These results indicate that adenoviruses containing prostate-specific promoters may express intended transgenes specifically in prostate in vivo.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalWorld Journal of Urology
Volume18
Issue number2
DOIs
StatePublished - Jan 1 2000

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Adenoviridae
Genetic Therapy
Prostate
Galactosidases
Mouse mammary tumor virus
Lac Operon
Terminal Repeat Sequences
Poisons
Transgenes
Heterografts
Urinary Bladder Neoplasms
Nude Mice
Canidae
Neoplasms
Prostatic Neoplasms
Antigens
Injections
Genes

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Transcriptionally regulated adenoviruses for prostate-specific gene therapy. / Lu, Yi; Steiner, Mitchell S.

In: World Journal of Urology, Vol. 18, No. 2, 01.01.2000, p. 93-101.

Research output: Contribution to journalArticle

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